Figure 2.

Proposed therapies to regenerate radiated salivary glands (SGs). Different epithelial cell types are maintained during homeostasis: ductal (intercalated, striated, granular convoluted tubule, and excretory), myoepithelial, and acinar cells. When glands are partially or globally injured, epithelial cells can undergo apoptosis and/or become functionally damaged. (1a) Reservoir cells of acinar and ductal compartments could then be transplanted post-radiation to locally repair the epithelia. (2a) Similarly, adipocytes, bone marrow (BM)-derived cells, mesenchymal stem cells (MSC) and/or amniotic cells can be transplanted, mobilized or intravenously (i.v.) delivered to aid in repair mechanisms. They can either participate in the formation of glandular cell types or stimulate radiation-surviving cells with their cellular secretome. (1b) After global SG damage, transplantation of multipotent SG specific epithelial stem/progenitors were shown to functionally and morphologically repair the tissue. (2b) Transplants of embryonic stem cells (ESC) and iPS (induced Pluripotent Stem cells) have also been explored to replace lost glandular cell types. (3) When SG are resected, in vitro tissue engineered organoids can be embedded in extracellular matrix and/or biomaterials and placed in the glandular bedding to connect with remaining tissue residues. Abbreviations: BM, bone marrow; MSC, mesenchymal stem cells; ESC, embryonic stem cells.